厘清吸烟与系统性硬化症之间的关系：对 EUSTAR 队列的分析。

Untangling the relationship between smoking and systemic sclerosis: an analysis of the EUSTAR cohort.

机构信息

Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy.

出版信息

RMD Open. 2024 May 20;10(2):e004101. doi: 10.1136/rmdopen-2024-004101.

DOI:10.1136/rmdopen-2024-004101

PMID:38772679

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11328649/

Abstract

OBJECTIVES

To untangle the association between smoking and systemic sclerosis (SSc).

METHODS

In the European Scleroderma Trials and Research cohort, the autoantibody status was compared between ever-smokers and never-smokers. Time until disease progression was assessed using Kaplan-Meier curves. Cox models were built to investigate the influence of smoking over 15 years of follow-up. All analyses were performed for the total cohort and stratified for sex and for positivity of anti-centromere (ACA) and anti-topoisomerase antibodies (ATA).

RESULTS

Overall, 12 314 patients were included in the study. Of these, 10 393 were women (84%), 4637 were ACA-positive (38%), 3919 were ATA-positive (32%) and 4271 (35%) were ever-smokers. In men, but not in women, smoking was associated with mortality (HR 1.63, 95% CI 1.23 to 2.16, p=0.001). Ever-smoking women were at higher risk for skin progression (HR 1.10, 95% CI 1.00 to 1.22, p=0.046) and for 'any organ progression' (HR 1.07, 95% CI 1.00 to 1.13, p=0.036). In women, 34% of never-smokers were ATA-positive compared with 21% of ever-smokers (p<0.001). In the group of ever-smokers, higher exposure rates, reflected by the number of pack-years (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) and by smoking duration (OR 0.96, 95% CI 0.95 to 0.97, p<0.001), were associated with lower frequency of ATA. In ACA-positive patients, the risk of mortality (HR 1.29, 95% CI 1.02 to 1.63, p=0.033), cardiac involvement (HR 1.25, 95% CI 1.03 to 1.43, p=0.001), skin progression (HR 1.21, 95% CI 1.03 to 1.42, p=0.018) and 'any organ progression' (HR 1.14, 95% CI 1.05 to 1.24, p=0.002) was increased among smokers. In ATA-positive smoking patients, mortality (HR 1.40, 95% CI 1.10 to 1.78, p=0.006), skin progression (HR 1.19, 95% CI 1.03 to 1.37, p=0.020) digital ulcers (HR 1.17, 95% CI 1.02 to 1.34, p=0.029) and 'any organ progression' (HR 1.11, 95% CI 1.00 to 1.22, p=0.048) occurred more frequently.

CONCLUSIONS

Our stratified analysis demonstrates that smoking is associated with an increased risk for mortality in male SSc patients but not in women. Strikingly, smoking is associated with lower prevalence of ATA positivity, in particular in women. In both ATA-positive and ACA-positive patients, smoking is a risk factor for mortality, skin progression and 'any organ progression'.

摘要

目的

厘清吸烟与系统性硬化症（SSc）之间的关联。

方法

在欧洲硬皮病试验和研究队列中，比较了曾经吸烟者和从不吸烟者的自身抗体状态。使用 Kaplan-Meier 曲线评估疾病进展的时间。建立 Cox 模型以研究吸烟对 15 年随访的影响。所有分析均针对总队列进行，并按性别以及抗着丝点（ACA）和抗拓扑异构酶抗体（ATA）的阳性情况进行分层。

结果

共有 12314 例患者纳入本研究。其中，10393 例为女性（84%），4637 例为 ACA 阳性（38%），3919 例为 ATA 阳性（32%），4271 例（35%）为曾经吸烟者。在男性中，但在女性中，吸烟与死亡率相关（HR 1.63，95%CI 1.23-2.16，p=0.001）。吸烟的女性发生皮肤进展的风险更高（HR 1.10，95%CI 1.00-1.22，p=0.046）和“任何器官进展”（HR 1.07，95%CI 1.00-1.13，p=0.036）的风险更高。在女性中，从未吸烟者中 ATA 阳性的比例为 34%，而曾经吸烟者中为 21%（p<0.001）。在曾经吸烟者中，更高的暴露率，反映在吸烟包年数（OR 0.98，95%CI 0.97-0.99，p<0.001）和吸烟持续时间（OR 0.96，95%CI 0.95-0.97，p<0.001），与 ATA 频率较低相关。在 ACA 阳性患者中，死亡率（HR 1.29，95%CI 1.02-1.63，p=0.033）、心脏受累（HR 1.25，95%CI 1.03-1.43，p=0.001）、皮肤进展（HR 1.21，95%CI 1.03-1.42，p=0.018）和“任何器官进展”（HR 1.14，95%CI 1.05-1.24，p=0.002）的风险在吸烟者中增加。在 ATA 阳性的吸烟患者中，死亡率（HR 1.40，95%CI 1.10-1.78，p=0.006）、皮肤进展（HR 1.19，95%CI 1.03-1.37，p=0.020）、手指溃疡（HR 1.17，95%CI 1.02-1.34，p=0.029）和“任何器官进展”（HR 1.11，95%CI 1.00-1.22，p=0.048）的发生率更高。